Bottom Line:
Rats fed CP had reduced plasma total homocysteine level and markedly increased levels of the choline pathway metabolites betaine, dimethylglycine, sarcosine, glycine and serine, as well as the transsulfuration pathway metabolites cystathionine and cysteine.In conclusion, the CP diet was associated with lower plasma homocysteine concentration and higher levels of serine, choline oxidation and transsulfuration metabolites compared to a casein diet.The status of related B-vitamins was also affected by CP.

ABSTRACTThe present study aimed to evaluate effects of a water-soluble protein fraction of chicken (CP), with a low methionine/glycine ratio, on plasma homocysteine and metabolites related to homocysteine metabolism. Male Wistar rats were fed either a control diet with 20% w/w casein as the protein source, or an experimental diet where 6, 14 or 20% w/w of the casein was replaced with the same amount of CP for four weeks. Rats fed CP had reduced plasma total homocysteine level and markedly increased levels of the choline pathway metabolites betaine, dimethylglycine, sarcosine, glycine and serine, as well as the transsulfuration pathway metabolites cystathionine and cysteine. Hepatic mRNA level of enzymes involved in homocysteine remethylation, methionine synthase and betaine-homocysteine S-methyltransferase, were unchanged, whereas cystathionine gamma-lyase of the transsulfuration pathway was increased in the CP treated rats. Plasma concentrations of vitamin B2, folate, cobalamin, and the B-6 catabolite pyridoxic acid were increased in the 20% CP-treated rats. In conclusion, the CP diet was associated with lower plasma homocysteine concentration and higher levels of serine, choline oxidation and transsulfuration metabolites compared to a casein diet. The status of related B-vitamins was also affected by CP.

Mentions:
Methionine serve as the precursor of the universal methyl donor S-adenosylmethionine (SAM), used in numerous methylation reactions throughout the body, with homocysteine (Hcy) being the end product [12]. The total amount of circulating homocysteine is referred to as total homocysteine (tHcy), and like the well-known lipid parameters, elevated circulating tHcy is also linked to increased risk of cardiovascular disease [13], though a causal relationship has been questioned due to the absence of clinical benefit after Hcy-lowering B-vitamin therapy [14]. Hcy has two metabolic fates. First, it can be permanently eliminated via the transsulfuration pathway to cystathionine and cysteine by the B6-dependent cystathionine beta-synthase (CBS) and cystathionine gamma lyase (CTH). Secondly, Hcy can be remethylated back to methionine either by methionine synthase (MS), which utilizes 5-methyltetrahydrofolate (mTHF) and cobalamin as cofactors, or by betaine-Hcy S-methyltransferase (BHMT), using betaine as the methyl donor [12]. BHMT-mediated remethylation of Hcy is linked to the choline oxidation pathway. In this reaction, betaine is converted to dimethylglycine (DMG), and further catabolized to sarcosine and glycine by the B2-dependent DMG dehydrogenase (DMGDH) and sarcosine dehydrogenase (SARDH), respectively [15,16]. Sarcosine can also be formed from glycine by the cytosolic enzyme glycine methyltransferase (GNMT), using SAM as methyl donor [17], and this is thought to modulate SAM levels by metabolizing excess SAM [18]. The interconversion between glycine and serine is provided by serine hydroxymethyltransferase (SHMT) [19]. The Hcy metabolism and the choline oxidation pathway are depicted in Figure 1.

Mentions:
Methionine serve as the precursor of the universal methyl donor S-adenosylmethionine (SAM), used in numerous methylation reactions throughout the body, with homocysteine (Hcy) being the end product [12]. The total amount of circulating homocysteine is referred to as total homocysteine (tHcy), and like the well-known lipid parameters, elevated circulating tHcy is also linked to increased risk of cardiovascular disease [13], though a causal relationship has been questioned due to the absence of clinical benefit after Hcy-lowering B-vitamin therapy [14]. Hcy has two metabolic fates. First, it can be permanently eliminated via the transsulfuration pathway to cystathionine and cysteine by the B6-dependent cystathionine beta-synthase (CBS) and cystathionine gamma lyase (CTH). Secondly, Hcy can be remethylated back to methionine either by methionine synthase (MS), which utilizes 5-methyltetrahydrofolate (mTHF) and cobalamin as cofactors, or by betaine-Hcy S-methyltransferase (BHMT), using betaine as the methyl donor [12]. BHMT-mediated remethylation of Hcy is linked to the choline oxidation pathway. In this reaction, betaine is converted to dimethylglycine (DMG), and further catabolized to sarcosine and glycine by the B2-dependent DMG dehydrogenase (DMGDH) and sarcosine dehydrogenase (SARDH), respectively [15,16]. Sarcosine can also be formed from glycine by the cytosolic enzyme glycine methyltransferase (GNMT), using SAM as methyl donor [17], and this is thought to modulate SAM levels by metabolizing excess SAM [18]. The interconversion between glycine and serine is provided by serine hydroxymethyltransferase (SHMT) [19]. The Hcy metabolism and the choline oxidation pathway are depicted in Figure 1.

Bottom Line:
Rats fed CP had reduced plasma total homocysteine level and markedly increased levels of the choline pathway metabolites betaine, dimethylglycine, sarcosine, glycine and serine, as well as the transsulfuration pathway metabolites cystathionine and cysteine.In conclusion, the CP diet was associated with lower plasma homocysteine concentration and higher levels of serine, choline oxidation and transsulfuration metabolites compared to a casein diet.The status of related B-vitamins was also affected by CP.

ABSTRACTThe present study aimed to evaluate effects of a water-soluble protein fraction of chicken (CP), with a low methionine/glycine ratio, on plasma homocysteine and metabolites related to homocysteine metabolism. Male Wistar rats were fed either a control diet with 20% w/w casein as the protein source, or an experimental diet where 6, 14 or 20% w/w of the casein was replaced with the same amount of CP for four weeks. Rats fed CP had reduced plasma total homocysteine level and markedly increased levels of the choline pathway metabolites betaine, dimethylglycine, sarcosine, glycine and serine, as well as the transsulfuration pathway metabolites cystathionine and cysteine. Hepatic mRNA level of enzymes involved in homocysteine remethylation, methionine synthase and betaine-homocysteine S-methyltransferase, were unchanged, whereas cystathionine gamma-lyase of the transsulfuration pathway was increased in the CP treated rats. Plasma concentrations of vitamin B2, folate, cobalamin, and the B-6 catabolite pyridoxic acid were increased in the 20% CP-treated rats. In conclusion, the CP diet was associated with lower plasma homocysteine concentration and higher levels of serine, choline oxidation and transsulfuration metabolites compared to a casein diet. The status of related B-vitamins was also affected by CP.